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Significance of Complement Activation in Alzheimer’s Disease
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Editor’s Recommendation
Plaque Complement Activation and Cognitive Loss in fold in AD versus other groups (all p ≤0.01). C9 staining was present
Alzheimer’s Disease on some diffuse plaques, and as on neuritic plaques. Bielschowsky-
Loeffler D, et al.
stained and complement-stained plaque counts were highly
J Neuroinflamm, 2008;5:9.
correlated, and were negatively correlated with cognitive measures.
When the Bielschowsky plaque count was used as a predictor, its
The objective of this study was to determine the relationship between correlations with cognitive measures were statistically significant, but
complement activation and cognition during the development of when iC3b and C9 plaque counts were added as additional
Alzheimer’s disease (AD). iC3b, C9, Bielschowsky, and Gallyas staining predictors, these correlations were not significant. This was attributed
was performed on aged normal (n=17), mild cognitively impaired to multicollinearity, i.e. both early-stage (iC3b) and late-stage (C9)
(n=12), and AD (n=17–18) inferior temporal gyrus specimens. Plaques complement activation occurs on neocortical plaques in subjects
were counted in 10x fields with high numbers of Bielschowsky-stained across the cognitive spectrum; contrary to previous reports, C9 is
plaques. One-way ANOVA was used to determine between-group present on some diffuse plaques. Because of high correlations
differences for plaque counts and measures of cognitive function, and between complement-stained and Bielschowsky-stained plaque
linear regression was used to evaluate global cognition as a function counts, quantitative assessment of the extent to which complement
of Bielschowsky-stained plaques. Terms for iC3b- and C9-stained activation mediates the relationship between plaques and cognitive
plaques were then added sequentially as additional predictors in a function could not be performed. Additional studies with animal
‘mediation analysis’ model. Complement was detected on plaques in models of AD (with late-stage complement activation), or a trial in AD
all groups, and on neurofibrillary tangles only in AD specimens. iC3b, patients with an inhibitor of late-stage complement activation, may
C9, and Bielschowsky-stained plaque counts increased 2.5- to three- be necessary to determine the significance of this process. ■
US NEUROLOGY 55
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